1. Field of the Invention
The present invention relates to the enhancement of the permeability into and through the skin of topically applied drugs.
2. Description of the Prior Art
The bio-activity of a wide variety of drugs render them attractive candidates for topical application to treat a number of conditions. Exemplary of such drugs and their applications are: acyclovir for topical treatment of herpes labilis and gentialis; trifluorothymidine for topical treatment of herpes infections; nitroglycerin (transdermal delivery) for prevention and treatment of anginal attacks; estradiol (and other estrogens) for treatment of various postmenopausal symptoms, such as osteoporosis and vasomotor disturbances; estradiol (and other estrogens) for contraceptive purposes; all-trans-retinoic acid (Tretinoin) for topical treatment of acne; clindamycin for topical treatment of acne; hydrocortisone (and other glucocorticoids) for topical treatment of anti-inflammtory conditions, etc.
Many of the drugs are only poorly absorbed through the skin of both human and non-human animals, however, thereby severely limiting their applicability. A number of agents which enhance the permeability through skin of several drugs have been proposed: Oleic acid--(Cooper, J. Pharm. Sci., Vol. 73, p. 1153 (1984); Loftsson et al, Pharm. Res., Vol. 4, p. 436 (1987));
Azone--(Spruance et al, Antimicrob. Agents Chemother., Vol. 26, p. 819 (1984);,
Dimethyl sulfoxide (DMSO)--(Freeman et al, Antimicrob. Agents Chemother., Vol. 29, p. 730 (1986);
Phosphine oxides--(Bodor and Loftsson, unpublished results);
Dimethylacetamide, dimethyl formamide, pyrrolidones and surfactants--(Barry, Dermatological
Formulations--Percutaneous Absorption, Chapter 4, Marcel Dekker, New York (1983)).
Some of the penetration enhancers are too toxic to be used in humans (e.g., dimethyl sulfoxide) or have irritating effects on the skin (e.g., oleic acid and phosphine oxides). In addition, most are not very effective as enhancers or are effective for only a limited number of drugs.
It is an object of the present invention to provide a novel composition and method for enhancing the permeability of topically applied bio-active agents or drugs through skin which are not subject to the above-noted drawbacks.